Psychoactive substances often bring about subjective (although these may be objectively observed) changes in consciousness and mood that the user may find rewarding and pleasant (e.g. euphoria) or advantageous (e.g. increased alertness) and are thus reinforcing. Substances which are both rewarding and positively reinforcing have the potential to induce a state of addiction – compulsive drug use despite negative consequences – when used consistently in excess. In addition, sustained use of some substances may produce a physical dependence or psychological dependence syndrome associated with somatic or psychological-emotional withdrawal states respectively. Drug rehabilitation aims to break this cycle of dependency, through a combination of psychotherapy, support groups, maintenance and even other psychoactive substances. However, the reverse is also true in some cases, that certain experiences on drugs may be so unfriendly and uncomforting that the user may never want to try the substance again. This is especially true of the deliriants (e.g. Jimson weed) and powerful dissociatives (e.g. Salvia divinorum). Most purely psychedelic drugs are considered to be non-addictive (e.g. LSD, psilocybin, mescaline). "Psychedelic amphetamines" or empathogen-entactogens (such as MDA and MDMA) may produce an additional stimulant or euphoriant effect, and thus have an addiction potential.

In part because of this potential for substance misuse, addiction, or dependence, the ethics of drug use is debated. Restrictions on drug production and sales in an attempt to decrease drug abuse is very common among national and sub-national governments worldwide. Ethical concerns have also been raised about over-use of these drugs clinically, and about their marketing by manufacturers.

Alcohol is a widely used and abused psychoactive drug. The global alcoholic drinks industry is expected to exceed $1 trillion this year.[2] Beer is the third-most popular drink overall, after water and tea.[3]

Psychoactive drug use can be traced to prehistory. There is archaeological evidence of the use of psychoactive substances (mostly plants) dating back at least 10,000 years, and historical evidence of cultural use over the past 5,000 years.[4] The chewing of coca leaves, for example, dates back over 8000 years ago in Peruvian society.[5][6]

Medicinal use is one important facet of psychoactive drug usage. However, some have postulated that the urge to alter one's consciousness is as primary as the drive to satiate thirst, hunger or sexual desire.[7] Supporters of this belief contend that the history of drug use and even children's desire for spinning, swinging, or sliding indicate that the drive to alter one's state of mind is universal.[8]

One of the first people to articulate this point of view, set aside from a medicinal context, was American author Fitz Hugh Ludlow (1836–1870) in his book The Hasheesh Eater (1857):

[D]rugs are able to bring humans into the neighborhood of divine experience and can thus carry us up from our personal fate and the everyday circumstances of our life into a higher form of reality. It is, however, necessary to understand precisely what is meant by the use of drugs. We do not mean the purely physical craving...That of which we speak is something much higher, namely the knowledge of the possibility of the soul to enter into a lighter being, and to catch a glimpse of deeper insights and more magnificent visions of the beauty, truth, and the divine than we are normally able to spy through the cracks in our prison cell. But there are not many drugs which have the power of stilling such craving. The entire catalog, at least to the extent that research has thus far written it, may include only opium, hashish, and in rarer cases alcohol, which has enlightening effects only upon very particular characters.[9]

This relationship is not limited to humans. A number of animals consume different psychoactive plants, animals, berries and even fermented fruit, becoming intoxicated, such as cats after consuming catnip. Traditional legends of sacred plants often contain references to animals that introduced humankind to their use.[10] Animals and psychoactive plants appear to have co-evolved, possibly explaining why these chemicals and their receptors exist within the nervous system.[11]

During the 20th century, many governments across the world initially responded to the use of recreational drugs by banning them and making their use, supply, or trade a criminal offense. A notable example of this was Prohibition in the United States, where alcohol was made illegal for 13 years. However, many governments, government officials and persons in law enforcement have concluded that illicit drug use cannot be sufficiently stopped through criminalization. Organizations such as Law Enforcement Against Prohibition (LEAP) have come to such a conclusion, believing:

[T]he existing drug policies have failed in their intended goals of addressing the problems of crime, drug abuse, addiction, juvenile drug use, stopping the flow of illegal drugs into this country and the internal sale and use of illegal drugs. By fighting a war on drugs the government has increased the problems of society and made them far worse. A system of regulation rather than prohibition is a less harmful, more ethical and a more effective public policy.[12][not in citation given]

In some countries, there has been a move toward harm reduction by health services, where the use of illicit drugs is neither condoned nor promoted, but services and support are provided to ensure users have adequate factual information readily available, and that the negative effects of their use be minimized. Such is the case of Portuguese drug policy of decriminalization, which achieved its primary goal of reducing the adverse health effects of drug abuse.[13]

Psychoactive substances are used by humans for a number of different purposes to achieve a specific end. These uses vary widely between cultures. Some substances may have controlled or illegal uses while others may have shamanic purposes, and still others are used medicinally. Other examples would be social drinking or sleep aids. Caffeine is the world's most widely consumed psychoactive substance, but unlike many others, it is legal and unregulated in nearly all jurisdictions. In North America, 90% of adults consume caffeine daily.[14]

Psychoactive drugs are divided into different groups according to their pharmacological effects. Commonly used psychoactive drugs and groups:

Depressants ("downers"), including sedatives, hypnotics, and narcotics. This category includes all of the calmative, sleep-inducing, anxiety-reducing, anesthetizing substances, which sometimes induce perceptual changes, such as dream images, and also often evoke feelings of euphoria.

Exposure to psychoactive drugs can cause changes to the brain that counteract or augment some of their effects; these changes may be beneficial or harmful. However, there is a significant amount of evidence that relapse rate of mental disorders negatively corresponds with length of properly followed treatment regimens (that is, relapse rate substantially declines over time), and to a much greater degree than placebo.[22]

Many psychoactive substances are used for their mood and perception altering effects, including those with accepted uses in medicine and psychiatry. Examples include caffeine, alcohol, cocaine, LSD, and cannabis.[23] Classes of drugs frequently used recreationally include:

Opioid analgesics, which also depress the central nervous system. These are used recreationally because of their euphoric effects.

Inhalants, in the forms of gas aerosols, or solvents, which are inhaled as a vapor because of their stupefying effects. Many inhalants also fall into the above categories (such as nitrous oxide which is also an analgesic).

In some modern and ancient cultures, drug usage is seen as a status symbol. Recreational drugs are seen as status symbols in settings such as at nightclubs and parties.[24] For example, in ancient Egypt, gods were commonly pictured holding hallucinogenic plants.[25]

Because there is controversy about regulation of recreational drugs, there is an ongoing debate about drug prohibition. Critics of prohibition believe that regulation of recreational drug use is a violation of personal autonomy and freedom.[26] In the United States, critics have noted that prohibition or regulation of recreational and spiritual drug use might be unconstitutional, and causing more harm than is prevented.[27]

Certain psychoactives, particularly hallucinogens, have been used for religious purposes since prehistoric times. Native Americans have used peyote cacti containing mescaline for religious ceremonies for as long as 5700 years.[28] The muscimol-containing Amanita muscaria mushroom was used for ritual purposes throughout prehistoric Europe.[29] Various other hallucinogens, including jimsonweed, psilocybin mushrooms, and cannabis, have been used in religious ceremonies for millennia.[30]

The use of entheogens for religious purposes resurfaced in the West during the counterculture movements of the 1960s and 70s. Under the leadership of Timothy Leary, new spiritual and intention-based movements began to use LSD and other hallucinogens as tools to access deeper inner exploration. In the United States, the use of peyote for ritual purposes is protected only for members of the Native American Church, which is allowed to cultivate and distribute peyote. However, the genuine religious use of peyote, regardless of one's personal ancestry, is protected in Colorado, Arizona, New Mexico, Nevada, and Oregon.[31]

Both military and civilian American intelligence officials are known to have used psychoactive drugs while interrogating captives apprehended in its War on Terror. In July 2012, Jason Leopold and Jeffrey Kaye, psychologists and human rights workers, had a Freedom of Information Act request fulfilled that confirmed that the use of psychoactive drugs during interrogation was a long-standing practice.[32][33] Captives and former captives had been reporting medical staff collaborating with interrogators to drug captives with powerful psychoactive drugs prior to interrogation since the very first captives' release.[34][35] In May 2003, recently released Pakistani captiveSha Mohammed Alikhel described the routine use of psychoactive drugs. He said that Jihan Wali, a captive kept in a nearby cell, was rendered catatonic through the use of these drugs.

The theory of dosage, set, and setting is a useful model in dealing with the effects of psychoactive substances, especially in a controlled therapeutic setting as well as in recreational use. Dr. Timothy Leary, based on his own experiences and systematic observations on psychedelics, developed this theory along with his colleagues Ralph Metzner, and Richard Alpert (Ram Dass) in the 1960s.[37]

Dosage

The first factor, dosage, has been a truism since ancient times, or at least since Paracelsus who said, "Dose makes the poison." Some compounds are beneficial or pleasurable when consumed in small amounts, but harmful, deadly, or evoke discomfort in higher doses.

Set

The set is the internal attitudes and constitution of the person, including their expectations, wishes, and fears. This factor is especially important for the hallucinogens, which have the ability to make conscious experiences out of the unconscious. In traditional cultures, set is shaped primarily by the worldview that all the members of the culture share.

Setting

The third aspect is setting, which pertains to the surroundings, the place, and the time in which the experiences transpire.

This theory clearly states that the effects are equally the result of chemical, pharmacological, psychological, and physical influences. The model that Timothy Leary proposed applied to the psychedelics, although it also applies to other psychoactives.[38]

Illustration of the major elements of neurotransmission. Depending on its method of action, a psychoactive substance may block the receptors on the post-synaptic neuron (dendrite), or block reuptake or affect neurotransmitter synthesis in the pre-synaptic neuron (axon).

Psychoactive drugs operate by temporarily affecting a person's neurochemistry, which in turn causes changes in a person's mood, cognition, perception and behavior. There are many ways in which psychoactive drugs can affect the brain. Each drug has a specific action on one or more neurotransmitter or neuroreceptor in the brain.

Drugs that increase activity in particular neurotransmitter systems are called agonists. They act by increasing the synthesis of one or more neurotransmitters, by reducing its reuptake from the synapses, or by mimicking the action by binding directly to the postsynaptic receptor. Drugs that reduce neurotransmitter activity are called antagonists, and operate by interfering with synthesis or blocking postsynaptic receptors so that neurotransmitters cannot bind to them.[39]

Exposure to a psychoactive substance can cause changes in the structure and functioning of neurons, as the nervous system tries to re-establish the homeostasis disrupted by the presence of the drug (see also, Neuroplasticity). Exposure to antagonists for a particular neurotransmitter can increase the number of receptors for that neurotransmitter or the receptors themselves may become more responsive to neurotransmitters; this is called sensitization. Conversely, overstimulation of receptors for a particular neurotransmitter may cause a decrease in both number and sensitivity of these receptors, a process called desensitization or tolerance. Sensitization and desensitization are more likely to occur with long-term exposure, although they may occur after only a single exposure. These processes are thought to play a role in drug dependence and addiction.[40]Physical dependence on antidepressants or anxiolytics may result in worse depression or anxiety, respectively, as withdrawal symptoms. Unfortunately, because clinical depression (also called major depressive disorder) is often referred to simply as depression, antidepressants are often requested by and prescribed for patients who are depressed, but not clinically depressed.

The following is a brief table of notable drugs and their primary neurotransmitter, receptor or method of action. It should be noted that many drugs act on more than one transmitter or receptor in the brain.[41]

Many professionals, self-help groups, and businesses specialize in drug rehabilitation, with varying degrees of success, and many parents attempt to influence the actions and choices of their children regarding psychoactives.[50]

The legality of psychoactive drugs has been controversial through most of recent history; the Second Opium War and Prohibition are two historical examples of legal controversy surrounding psychoactive drugs. However, in recent years, the most influential document regarding the legality of psychoactive drugs is the Single Convention on Narcotic Drugs, an international treaty signed in 1961 as an Act of the United Nations. Signed by 73 nations including the United States, the USSR, India, and the United Kingdom, the Single Convention on Narcotic Drugs established Schedules for the legality of each drug and laid out an international agreement to fight addiction to recreational drugs by combatting the sale, trafficking, and use of scheduled drugs.[53] All countries that signed the treaty passed laws to implement these rules within their borders. However, some countries that signed the Single Convention on Narcotic Drugs, such as the Netherlands, are more lenient with their enforcement of these laws.[54]

In the United States, the Food and Drug Administration (FDA) has authority over all drugs, including psychoactive drugs. The FDA regulates which psychoactive drugs are over the counter and which are only available with a prescription.[55] However, certain psychoactive drugs, like alcohol, tobacco, and drugs listed in the Single Convention on Narcotic Drugs are subject to criminal laws. The Controlled Substances Act of 1970 regulates the recreational drugs outlined in the Single Convention on Narcotic Drugs.[56] Alcohol is regulated by state governments, but the federal National Minimum Drinking Age Act penalizes states for not following a national drinking age.[57] Tobacco is also regulated by all fifty state governments.[58] Most people accept such restrictions and prohibitions of certain drugs, especially the "hard" drugs, which are illegal in most countries.[59][60][61]

In the medical context, psychoactive drugs as a treatment for illness is widespread and generally accepted. Little controversy exists concerning over the counter psychoactive medications in antiemetics and antitussives. Psychoactive drugs are commonly prescribed to patients with psychiatric disorders. However, certain critics believe that certain prescription psychoactives, such as antidepressants and stimulants, are overprescribed and threaten patients' judgement and autonomy.[62][63]

^Robert Beckhusen (2012-07-11). "U.S. Injected Gitmo Detainees With ‘Mind Altering’ Drugs". Wired magazine. Archived from the original on 2012-07-14. Retrieved 2012-07-14. That’s according to a recently declassified report (.pdf) from the Pentagon’s inspector general, obtained by Truthout‘s Jeffrey Kaye and Jason Leopold after a Freedom of Information Act Request. In it, the inspector general concludes that “certain detainees, diagnosed as having serious mental health conditions being treated with psychoactive medications on a continuing basis, were interrogated.” The report does not conclude, though, that anti-psychotic drugs were used specifically for interrogation purposes.

^Haroon Rashid (2003-05-23). "Pakistani relives Guantanamo ordeal". BBC News. Archived from the original on 2012-07-14. Retrieved 2009-01-09. Mr Shah alleged that the Americans had given him injections and tablets prior to interrogations. "They used to tell me I was mad," the 23-year-old told the BBC in his native village in Dir district near the Afghan border. I was given injections at least four or five times as well as different tablets. I don't know what they were meant for."

^Meek, James (2003-12-03). "People the law forgot". London: The Guardian. Archived from the original on 2012-07-14. Retrieved 2012-07-14. The biggest damage is to my brain. My physical and mental state isn't right. I'm a changed person. I don't laugh or enjoy myself much.